Circulating angiotensin-(1-7) is decreased in patients with isolated nocturnal hypertension.

Isolated nocturnal hypertension (INHT), defined as nighttime elevated blood pressure (BP) with normal daytime BP assessed by ambulatory BP monitoring, is associated with higher cardiovascular morbidity and mortality. We hypothesized that an alteration in the circulating renin-angiotensin system (RAS) contributes to INHT development. We examined circulating levels of angiotensin (Ang) (1-7) and Ang II and ACE2 activity in 26 patients that met the INHT criteria, out of 50 that were referred for BP evaluation (62% women, 45 ±â€Š16 years old). Those with INHT were older, had a higher BMI, lower circulating Ang-(1-7) (P = 0.002) and Ang II levels (P = 0.02) and no change in ACE2 activity compared to those normotensives. Nighttime DBP was significantly correlated with Ang-(1-7) and Ang II levels. Logistic regression showed significant association in Ang-(1-7) and Ang II levels with INHT. Our study reveals differences in circulating RAS in individuals with INHT.

[Congenital neutropenia type IV: case report]. / Neutropenia congénita de tipo IV: reporte de un caso.

Severe congenital neutropenia (SCN) is a heterogeneous disease whose more common feature is an absolute neutrophil count less than 0.5 x 109/l. It presents great genetic heterogeneity. Autosomal dominant inherited mutations of the elastase 2 gene (ELA2) represent the most common etiology. The first choice treatment is the administration of granulocyte colony stimulating factor. Patients with SCN develop severe infections early in life. We present a patient who associated SCN to a peculiar phenotype, characterized by triangular facies, retromicrognathia, prominent venous pattern in the lower limbs, atrial septal defect and poor weight progress, in whom a deficiency of the enzyme glucose 6 phosphate dehydrogenase, Neutropenia congénita de tipo IV: reporte de un caso Congenital neutropenia type IV: case report a catalytic subunit 3 (G6PC3), was diagnosed. Despite the infrequency of this mutation as the origin of SCN (2%), its knowledge becomes important because the coexistence of the characteristic phenotype and SCN guides the request for the genetic study that allows reaching the diagnosis.

La neutropenia congénita grave (NCG) es una entidad heterogénea cuya característica común es un recuento absoluto de neutrófilos inferior a 0,5 x 109/l. Presenta gran heterogeneidad genética, las mutaciones más frecuentes son las del gen de la elastasa 2 (ELA 2). El tratamiento de primera elección es la administración de factor estimulador de colonias de granulocitos. Los pacientes con NCG presentan infecciones graves en etapas tempranas de la vida. Se presenta una paciente con NCG asociada a fenotipo peculiar con facies triangular, retromicrognatia, patrón venoso prominente en miembros inferiores, comunicación interauricular y mal progreso ponderal, en quien se diagnosticó déficit de la enzima glucosa 6 fosfato deshidrogenasa, subunidad catalítica 3 (G6PC3). A pesar de lo infrecuente de esta mutación como causa de NCG (2 %), su conocimiento cobra importancia porque la coexistencia del fenotipo característico con una NCG orienta en la solicitud del estudio genético que permite arribar al diagnóstico.

Neutropenia congénita de tipo IV: reporte de un caso / Congenital neutropenia type IV: case report

La neutropenia congénita grave (NCG) es una entidad heterogénea cuya característica común es un recuento absoluto de neutrófilos inferior a 0,5 x 10 9/l. Presenta gran heterogeneidad genética, las mutaciones más frecuentes son las del gen de la elastasa 2 (ELA 2). El tratamiento de primera elección es la administración de factor estimulador de colonias de granulocitos. Los pacientes con NCG presentan infecciones graves en etapas tempranas de la vida. Se presenta una paciente con NCG asociada a fenotipo peculiar con facies triangular, retromicrognatia, patrón venoso prominente en miembros inferiores, comunicación interauricular y mal progreso ponderal, en quien se diagnosticó déficit de la enzima glucosa 6 fosfato deshidrogenasa, subunidad catalítica 3 (G6PC3). A pesar de lo infrecuente de esta mutación como causa de NCG (2 %), su conocimiento cobra importancia porque la coexistencia del fenotipo característico con una NCG orienta en la solicitud del estudio genético que permite arribar al diagnóstico.

Severe congenital neutropenia (SCN) is a heterogeneous disease whose more common feature is an absolute neutrophil count less than 0.5 x 10 9/l. It presents great genetic heterogeneity. Autosomal dominant inherited mutations of the elastase 2 gene (ELA2) represent the most common etiology. The first choice treatment is the administration of granulocyte colony stimulating factor. Patients with SCN develop severe infections early in life. We present a patient who associated SCN to a peculiar phenotype, characterized by triangular facies, retromicrognathia, prominent venous pattern in the lower limbs, atrial septal defect and poor weight progress, in whom a deficiency of the enzyme glucose 6 phosphate dehydrogenase, a catalytic subunit 3 (G6PC3), was diagnosed. Despite the infrequency of this mutation as the origin of SCN (2%), its knowledge becomes important because the coexistence of the characteristic phenotype and SCN guides the request for the genetic study that allows reaching the diagnosis.

New obstetric systemic inflammatory response syndrome criteria for early identification of high-risk of sepsis in obstetric patients.

OBJECTIVES: We aimed to establish new cut-off values for SIRS (Systemic Inflammatory Response Syndrome) variables in the obstetric population. METHODS: A prospective cohort study in pregnant and postpartum women admitted with systemic infections between December 2017 and January 2019. Patients were divided into three cohorts: Group A, patients with infection but without severe maternal outcomes (SMO); Group B, patients with infection and SMO or admission to the intensive care unit (ICU); and Group C, a control group. Outcome measures were ICU admission and SMO. The relationship between SIRS criteria and SMO was expressed as the area under the receiver operating characteristics curve (AUROC), selecting the best cut-off for each SIRS criterion. RESULTS: A total of 541 obstetric patients were enrolled, including 341 with infections and 200 enrolled as the reference group (Group C). The patients with infections included 313 (91.7%) in Group A and 28 (8.2%) in Group B. There were significant differences for all SIRS variables in Group B, compared with Groups A and C, but there were no significant differences between Groups A and C. The best cut-off values were the following: temperature 38.2 °C, OR 4.1 (1.8-9.0); heart rate 120 bpm, OR 2.9 (1.2-7.4); respiratory rate 22 bpm, OR 4.1 (1.6-10.1); and leukocyte count 16,100 per mcl, OR 3.5 (1.6-7.6). CONCLUSIONS: The cut-off values for SIRS variables did not differ between healthy and infected obstetric patients. However, a higher cut-off may help predict the population with a higher risk of severe maternal outcomes.

Distribution of molecular subtypes of advanced lung adenocarcinoma and clinical outcomes in a center of Argentina.

The prevalence of relevant oncogenic drivers in lung adenocarcinoma varies in our region and data on clinical outcomes is scarce. The objective of the study was to describe the prevalence of KRAS, BRAF and EGFR mutations and ALK translocations in patients with advanced lung adenocarcinoma, and to depict the clinical outcome according to treatment strategies. Patients with adequate tumor biopsy sampling were included. KRAS, BRAF and EGFR mutations were studied by Sanger sequencing. ALK translocations were studied by fluorescent in situ hybridization (FISH) and immunohistochemistry (IH) with antibodies against ALK with clones D5F3 and 5A4. Informed consent was signed by 118 patients and 84 (72%) with complete molecular analysis were included. KRAS mutations were detected in 16 samples (19%), EGFR in 11 (13%), 9 of them conferring sensitivity to EGFR inhibitors, and BRAF mutations in 1 (1%). ALK translocations were detected in 3 samples (4%). Median follow-up was 42.4 [interquartile range (IQR): 27.0-64.2] months. Globally, median overall survival was 10.3 [IQR: 5.6-20.2] months. Median survival was 10.8 [IQR: 6.0-20.3] months in the group of patients without detectable molecular alteration, 9.6 [IQR: 3.7-16.1] months in KRAS mutant population (HR: 1.08; p = 0.82) and 32.5 [IQR: 19.6-38.4] months in patients with ALK translocations or sensitizing EGFR mutated tumors treated with tyrosine kinase inhibitors (HR: 0.27; p = 0.03). In conclusion, the prevalence of molecular alterations and outcomes in our population is similar to that reported in other studies in Western countries.

Distribution of molecular subtypes of advanced lung adenocarcinoma and clinical outcomes in a center of Argentina

The prevalence of relevant oncogenic drivers in lung adenocarcinoma varies in our region and data on clinical outcomes is scarce. The objective of the study was to describe the prevalence of KRAS, BRAF and EGFR mutations and ALK translocations in patients with advanced lung adenocarcinoma, and to depict the clinical outcome according to treatment strategies. Patients with adequate tumor biopsy sampling were included. KRAS, BRAF and EGFR mutations were studied by Sanger sequencing. ALK translocations were studied by fluorescent in situ hybridization (FISH) and immunohistochemistry (IH) with antibodies against ALK with clones D5F3 and 5A4. Informed consent was signed by 118 patients and 84 (72%) with complete molecular analysis were included. KRAS mutations were detected in 16 samples (19%), EGFR in 11 (13%), 9 of them conferring sensitivity to EGFR inhibitors, and BRAF mutations in 1 (1%). ALK translocations were detected in 3 samples (4%). Median follow-up was 42.4 [interquartile range (IQR): 27.0-64.2] months. Globally, median overall survival was 10.3 [IQR: 5.6-20.2] months. Median survival was 10.8 [IQR: 6.0-20.3] months in the group of patients without detectable molecular alteration, 9.6 [IQR: 3.7-16.1] months in KRAS mutant population (HR: 1.08; p = 0.82) and 32.5 [IQR: 19.6-38.4] months in patients with ALK translocations or sensitizing EGFR mutated tumors treated with tyrosine kinase inhibitors (HR: 0.27; p = 0.03). In conclusion, the prevalence of molecular alterations and outcomes in our population is similar to that reported in other studies in Western countries.

La prevalencia de alteraciones en oncogenes en adenocarcinoma de pulmón varía en nuestra región. El objetivo fue describir la prevalencia de mutaciones en KRAS, BRAF y EGFR y las translocaciones de ALK en pacientes con adenocarcinoma de pulmón y estudiar la supervivencia de acuerdo a subtipos moleculares. Se incluyeron pacientes con biopsias adecuadas para el estudio. Se evaluó el estado mutacional de KRAS, BRAF y EGFR por secuenciación con la técnica de Sanger. Las translocaciones de ALK se estudiaron por hibridación in situ por fluorescencia (FISH) e inmunohistoquimica (IHQ) contra ALK (clones D5F3 y 5A4). De 118 pacientes evaluados, se incluyeron 84 (72%) con análisis molecular completo. Se detectaron mutaciones de KRAS en 16 muestras (19%), EGFR en 11 (13%), y BRAF en 1 muestra (1%). Se detectaron rearreglos de ALK en 3 muestras (4%). La mediana de seguimiento de los pacientes fue de 42.4 [rango intercuatilo (RIC): 27.0-64.2] meses. Globalmente, la mediana de supervivencia en la población fue 10.3 [RIC: 5.6-20.2] meses y fue de 10.8 [RIC: 6.0 20.3] meses en pacientes sin alteraciones moleculares detectables. La mediana de supervivencia de los pacientes con mutación en KRAS fue de 9.6 [RIC: 3.7-16.1] meses (HR: 1.08; p = 0.82) y 32.5 [RIC: 19.6-38.4] meses en el grupo con rearreglos de ALK o mutaciones en EGFR tratados con inhibidores de tirosina quinasa (HR: 0.27; p = 0.03). En conclusión, la prevalencia de alteraciones moleculares en nuestra población fue similar a otros países occidentales.

Podocitopatía lúpica / Lupus podocytopathy

El lupus eritematoso sistémico (LES) es una enfermedad sistémica autoinmune que puede afectar a múltiples órganos. Aproximadamente el 50% de los pacientes con LES desarrollan enfermedad renal clínicamente evidente, la cual es una causa importante de morbimortalidad. El síndrome nefrótico (SN) es frecuente en los pacientes con nefritis lúpica (NL) y usualmente se asocia a depósitos de complejos inmunes en las paredes capilares, acompañados de proliferación endocapilar y necrosis. No obstante, existe un número creciente de casos reportados de pacientes con LES y SN cuyas biopsias se caracterizan por injuria podocitaria, consistente en fusión pedicelar en la microscopía electrónica y un patrón morfológico idéntico a la enfermedad por cambios mínimos (ECM), a la esclerosis focal y segmentaria primaria o a una glomerulonefritis proliferativa mesangial, en ausencia de depósitos inmunes en las paredes capilares. Este hallazgo podría deberse a la coexistencia de NL y ECM, sin embargo, la mayoría de las investigaciones consideran que esto no es una mera coincidencia. De allí surge una nueva entidad, la "podocitopatía lúpica", patología posiblemente mediada por la activación de células T y la presencia de un factor de permeación glomerular. Esto permite diferenciar al grupo de pacientes con LES y SN, que en la biopsia carecen de depósitos inmunes en las paredes capilares o de signos de actividad lúpica renal, se evidencia fusión pedicelar difusa en la ME y presentan además una alta sensibilidad al tratamiento con corticoides. El diagnóstico de esta nueva entidad, requiere de la interpretación de los hallazgos histopatológicos con la correcta integración de los datos de la inmunofluorescencia y la microscopía electrónica

Lupus Erythematosus (SLE) is a systemic autoimmune disease which may affect several organs. Approximately 50% of SLE patients develop clinically overt renal disease, an important cause of morbidity and mortality. Nephrotic syndrome (NS) is frequent in patients suffering from lupus nephritis (LN) and it is usually associated with immune complex deposition on capillary walls accompanied by endocapillary proliferation and necrosis. However, a growing number of reported cases of SLE and NS patients show biopsies which reveal podocyte injury, consisting of pedicel fusion upon electron microscopy and a morphological pattern identical to minimal change disease (MCD), primary focal segmental glomerulosclerosis or mesangial proliferative glomerulonephritis, in absence of immune complex deposition on capillary walls. Although this finding could be explained by the coexistence of LN and MCD, most researchers consider that this fact is not pure coincidence. A new term, lupus podocytopathy, therefore appears to define a distinct entity characterized by T cell activation and the presence of a glomerular permeability factor. This allows to distinguish the group of SLE and NS patients whose biopsies do not show immune complex deposition on capillary walls or signs of renal lupus activity; electron microscopy reveals diffuse pedicel fusion and patients show high responsiveness to corticosteroid treatment. In order to diagnose this new entity, it is necessary to interpret histopathological findings together with data gathered from immunofluorescence and electron microscopy

Prevalence of Aminoglycoside-Modifying Enzymes in Escherichia coli and Klebsiella pneumoniae Producing Extended Spectrum ß-Lactamases Collected in Two Multicenter Studies in Spain.

The in vitro activity of amikacin, gentamicin, kanamycin, tobramycin, neomycin, and netilmicin against 420 Escherichia coli producing extended spectrum ß-lactamases (Ec-ESBLs) and 139 Klebsiella pneumoniae producing extended spectrum ß-lactamase (Kp-ESBL) collected in two multicenter studies performed in Spain in 2000 and 2006 was determined. The presence of genes encoding aminoglycoside-modifying enzymes (AMEs) and 16S ribosomal RNA (rRNA) methylases [aac(3)-Ia, aac(3)-IIa, aac(3)-IVa, aac(6')-Ib, ant(2")-Ia, ant(4')-IIa, aph(3')-Ia, aph(3')-IIa, armA, rmtB, and rmtC] was also investigated. The resistance to (one or more) aminoglycosides was significantly higher in Kp-ESBL (104/139, 74.8%) than in Ec-ESBL (171/420, 40.7%; p < 0.0001). The lowest resistance rates for both species in the two studies were observed for amikacin. The prevalence of AME genes was significantly different in Ec-ESBL (161/420, 38.3%) than in Kp-ESBL (115/139, 82.7%; p < 0.0001). The most prevalent AME genes in Ec-ESBL and Kp-ESBL were aac(6')-Ib (16.2% and 44.6%) and aac(3)-IIa (14.7% and 43.1%), respectively. The expected phenotypic profile correlated with the found AMEs encoding genes in 59.6% Ec-ESBL and 26.1% Kp-ESBL. In Ec-ESBL, aac(6')-Ib was usually associated in 2000 with blaSHV (26.6%), but with blaCTX-M-1 group (34.8%) in 2006, while aac(3)-IIa was coincident in 2000 with blaTEM (14.6%) and with blaCTX-M-1 group (16.3%) in 2006. Among Kp-ESBL, the aac(6')-Ib and aac(3)-IIa genes were more frequent in strains with blaTEM (22.0% and 44.0%) in 2000 and with blaCTX-M-1 group (46.4% and 34.0%) in 2006. Resistance to aminoglycosides in Ec-ESBL and Kp-ESBL is frequent and related to production of AMEs; this limits the clinical use of aminoglycosides against these organisms.

Performance Assessment of Epidermal Growth Factor Receptor Gene Sequencing According to Sample Size in Daily Practice Conditions.

Lung carcinoma is the main cause of cancer death worldwide. Adenocarcinoma molecular biomarkers have been discovered, and targeted therapies have been developed with encouraging results. The epidermal growth factor receptor gene is one of these biomarkers. Exons 18 to 21 should be studied in patients with advanced adenocarcinoma, who are candidates for treatment with tyrosine kinase inhibitors. The objective was to compare the performance of the determination in large and small samples in daily practice conditions, trying to adjust to published consensus guidelines. A retrospective observational study of 141 cases was carried out, with exons 19 and 21 sequencing. Sample size (small vs. large), including number of satisfactory polymerase chain reaction (PCR), sequencing, deletions, and mutations, were evaluated. In small biopsies, sample type, fragment number, and percentage of tumor per sample were analyzed. The results shown 114/141 (80.8) cases that met selection criteria; 60/114 (53%) were large (surgical) and 54/114 (47%) were small samples (19/54 endoscopic, 17/54 fine needle aspiration clots, 4/54 lymph nodes, 14/54 core and other). All large samples were satisfactory PCR, 56/60 (93%) satisfactory sequencing, and 12/56 (21%) had deletions in exon 19. Small samples were satisfactory PCRs in 50/54 (93%) cases, and satisfactory sequencing in 35/50 (65%), 8/35 (23%) showed alterations in exon 19, and 1/35 (3%) in exon 21. In conclusion, the proportion of samples unfit for the study of the epidermal growth factor receptor gene mutational status increased from 7% in large samples to 35% in small ones. Nineteen small samples were inconclusive, with cell blocks predominating, 10/19 (53%).

Factores de riesgo predictores de la necesidad del uso de insulina en pacientes con diabetes gestacional / Predictive risk factors of insulin use requirement in patients with gestational diabetes

La diabetes gestacional (DMG) es la alteración de la tolerancia a la glucosa que comienza o es reconocida por primera vez durante el embarazo en curso. Un mal control glucémico aumenta el riesgo de complicaciones materno-fetales severas, por lo cual el manejo estricto de la DMG es primordial para prevenirlas. La elección del tratamiento con plan nutricional o insulina depende fundamentalmente de los objetivos glucémicos alcanzados, y reconocer los factores de riesgo predictores de su fracaso permite optimizar este manejo

Tuberculosis y actinomicosis: Un caso pediatrico de comorbilidad / Pulmonary actinomycosis and tuberculosis: A comorbidity pediatric case

La actinomicosis es una infección supurativa crónica, producida por bacterias Gram-positivas anaeróbicas o especies Actinomyces microaerófilas. Es rara en niños y adolescentes; es más común en inmunodeprimidos. El Mycobacterium tuberculosis colabora en el desarrollo de la enfermedad. La afectación pulmonar aparece como un cuadro de condensación crónica que no mejora con el tratamiento antibiótico convencional. Las complicaciones clásicas de afectación de la pared torácica con fistulización y supuración en «granulo de azufre¼ son descritas con menor frecuencia en la actualidad. El diagnóstico es un verdadero desafío y se establece mediante el aislamiento de las especies de Actinomyces. El tratamiento de elección para todas las formas clínicas de la enfermedad es el uso prolongado de antibióticos. Objetivo. Presentar un caso pediátrico de comorbilidad entre tuberculosis y actinomicosis. Resaltar la importancia de la sospecha diagnóstica de actinomicosis frente a todo proceso supurado crónico.

Actinomycosis is a chronic suppurative infection, produced by anaerobic Gram-positive bacteria or microaerobic Actinomyces species. It is rare in children and adolescents and it is more common in immunocompromised. Mycobacterium tuberculosis collaborates on the development of the disease. Pulmonary involvement appears as a picture of chronic condensation that does not improve with conventional antibiotic treatment. Classic complications affecting the thoracic wall with drainage in «sulfur granule¼ and fistulization are described less frequently nowadays. The diagnosis is a real challenge and it is set by using the isolation of species of Actinomyces. The treatment of choice for all clinical forms of the disease is the prolonged use of antibiotics. Objective: to present a pediatric case of comorbidity between tuberculosis and actinomycosis and to highlight the importance of diagnostic suspicion of actinomycosis in the presence of all chronic suppurative processes.

Skeletal involvement in Gaucher disease: An observational multicenter study of prognostic factors in the Argentine Gaucher disease patients.

Patients with Gaucher type 1 (GD1) throughout Argentina were enrolled in the Argentine bone project to evaluate bone disease and its determinants. We focused on presence and predictors of bone lesions (BL) and their relationship to therapeutic goals (TG) with timing and dose of enzyme replacement therapy (ERT). A total of 124 patients on ERT were enrolled in a multi-center study. All six TG were achieved by 82% of patients: 70.1% for bone pain and 91.1% for bone crisis. However, despite the fact that bone TGs were achieved, residual bone disease was present in 108 patients on ERT (87%) at time 0. 16% of patients showed new irreversible BL (bone infarcts and avascular osteonecrosis) despite ERT, suggesting that they appeared during ERT or were not detected at the moment of diagnosis. We observed 5 prognostic factors that predicted a higher probability of being free of bone disease: optimal ERT compliance; early diagnosis; timely initiation of therapy; ERT initiation dose ≥45 UI/kg/EOW; and the absence of history of splenectomy. Skeletal involvement was classified into 4 major phenotypic groups according to BL: group 1 (12.9%) without BL; group 2 (28.2%) with reversible BL; group 3 (41.9%) with reversible BL and irreversible chronic BL; and group 4 (16.9%) with acute irreversible BL. Our study identifies prognostic factors for achieving best therapeutic outcomes, introduces new risk stratification for patients and suggests the need for a redefinition of bone TG. Am. J. Hematol. 91:E448-E453, 2016. © 2016 Wiley Periodicals, Inc.

[Pulmonary actinomycosis and tuberculosis. A comorbidity pediatric case]. / Tuberculosis y actinomicosis. Un caso pediatrico de comorbilidad.

UNLABELLED: Actinomycosis is a chronic suppurative infection, produced by anaerobic Gram-positive bacteria or microaerobic Actinomyces species. It is rare in children and adolescents and it is more common in immunocompromised. Mycobacterium tuberculosis collaborates on the development of the disease. Pulmonary involvement appears as a picture of chronic condensation that does not improve with conventional antibiotic treatment. Classic complications affecting the thoracic wall with drainage in «sulfur granule¼ and fistulization are described less frequently nowadays. The diagnosis is a real challenge and it is set by using the isolation of species of Actinomyces. The treatment of choice for all clinical forms of the disease is the prolonged use of antibiotics. OBJECTIVE: to present a pediatric case of comorbidity between tuberculosis and actinomycosis and to highlight the importance of diagnostic suspicion of actinomycosis in the presence of all chronic suppurative processes.

La actinomicosis es una infección supurativa crónica, producida por bacterias Gram-positivas anaeróbicas o especies Actinomyces microaerófilas. Es rara en niños y adolescentes; es más común en inmunodeprimidos. El Mycobacterium tuberculosis colabora en el desarrollo de la enfermedad. La afectación pulmonar aparece como un cuadro de condensación crónica que no mejora con el tratamiento antibiótico convencional. Las complicaciones clásicas de afectación de la pared torácica con fistulización y supuración en «granulo de azufre¼ son descritas con menor frecuencia en la actualidad. El diagnóstico es un verdadero desafío y se establece mediante el aislamiento de las especies de Actinomyces. El tratamiento de elección para todas las formas clínicas de la enfermedad es el uso prolongado de antibióticos. Objetivo. Presentar un caso pediátrico de comorbilidad entre tuberculosis y actinomicosis. Resaltar la importancia de la sospecha diagnóstica de actinomicosis frente a todo proceso supurado crónico.

Lesiones por virus de papiloma humano de la vía aerodigestiva superior, incidencia de subtipos / Human papilloma virus related lesions of the upper aerodigestive tract, incidence of subtypes / Lesões por vírus do papiloma humano do trato aerodigestivo superior - Incidência de subtipos

Antecedentes: el cáncer de la vía aerodigestiva superior (CVADS), al que con frecuencia se lo engloba como “cáncer de cabeza y cuello”, tiene una incidencia aproximada de 30 nuevos casos cada 100.000 habitantes por año, habiendo presentado un aumento significativo en la última década. Los principales factores de riesgo para el CVADS siguen siendo la exposición al tabaco y el alcohol, pero el virus del papiloma humano (VPH) se ha encontrado asociado en la etiología del 20 al 25% de los CVADS, principalmente los ubicados en la región de la orofaringe. El virus tiene dos oncoproteínas, E6 y E7. E6 tiene la propiedad de unirse a la proteína celular p53, que regula la transcripción de la p21 e inhibe las quinasas ciclindependientes, las cuales son esenciales para la progresión del ciclo celular a la fase S, haciendo que la célula se replique descontroladamente...

Background: cancer of the upper aerodigestive tract (cuadt) that often encompasses it as “cancer of the head and neck, has an incidence of 30 new cases per 100,000 population per year, having presented a significant increase in the last decade. The main risk factors for CUADT remain exposure to tabaco and alcohol, but the human papillomavirus (HPV) has been found associated in the etiology of 20 to 25% of CUADT, mainly those located in the region oropharynx. The virus has two oncoproteins E6 and E7. E6 has the property of binding to cellular p53 protein that regulates transcription of p21, which inhibits cyclin dependent-kinases which are essential for cell cycle progression to S phase causing the cell to replicate uncontrollably...

Antecedentes: o câncer do trato aerodigestivo superior, que é frequentemente englobado no “câncer de cabeça e pescoço”, tem uma incidência aproximada de 30 casos novos cada 100.000 habitantes por ano, com um incremento significativo na última dé- cada. Os principais fatores de risco para o câncer de cabeça e de pescoço continuam sendo a exposição ao tabaco e ao álcool, mas o vírus do papiloma humano (VPH) é associado na etiologia de 20% até 25% dos casos de câncer do trato aerodigestivo superior, principalmente nos localizados na região da orofaringe. O vírus contém duas oncoproteínas E6 e E7. A E6 tem a propriedade de se unir à proteí- na celular p53, a qual regula a transcrição da p21, a qual inibe as quinases dependentes de ciclina que são essenciais para a progressão do ciclo celular à fase S, fazendo com que a célula se replique descontroladamente...

Tuberculosis cutánea: reporte de un caso / Cutaneous tuberculosis: case report

Se denomina tuberculosis cutánea a la enfermedad cutánea infecciosa crónica ocasionada por el Mycobacterium tuberculosis. Es poco frecuente y particularmente difícil de diagnosticar. Su incidencia, según la bibliografía, oscila entre el 1,5 y el 4% de todas las formas de tuberculosis extrapulmonares. Las formas clínicas dependen de la vía de llegada del bacilo a la piel, del estado inmunológico del paciente y del medio ambiente. Se presenta un caso de tuberculosis cutánea en un niño con lesiones dermatológicas crónicas, de evolución tórpida, sin respuesta a los tratamientos instituidos, la biopsia de piel mostró granulomas caseosos. El objetivo es describir un paciente con una presentación clínica infrecuente de esta enfermedad, destacar la importancia de su reconocimiento y tratamiento precoz, y evitar así la aparición de complicaciones y secuelas.

Cutaneous tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. It is not very frequent and particularly difficult to diagnose. It incidence ranges between 1.5 and 4% of all extrapulmonary tuberculosis, according to bibliography. The clinic presentations depend on the arrival via of the bacillus to the skin, the patient's immune state and the environment. We show a cutaneous tuberculosis on a child with chronic dermatologic lesions, with torpid evolution, without response to treatments; the skinbiopsy showed caseous granulomas. The aim is to show a patient with an infrequent clinic presentation of this disease, to emphasize the importance of an early recognition and treatment, avoiding the appearance of complications and sequels.

[Cutaneous tuberculosis: case report]. / Tuberculosis cutánea: reporte de un caso.

Cutaneous tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. It is not very frequent and particularly difficult to diagnose. It incidence ranges between 1.5 and 4% of all extrapulmonary tuberculosis, according to bibliography. The clinic presentations depend on the arrival via of the bacillus to the skin, the patient's immune state and the environment. We show a cutaneous tuberculosis on a child with chronic dermatologic lesions, with torpid evolution, without response to treatments; the skin biopsy showed caseous granulomas. The aim is to show a patient with an infrequent clinic presentation of this disease, to emphasize the importance of an early recognition and treatment, avoiding the appearance of complications and sequels.

GEN MDR-1 y resistencia al imatinib en células K562 / MDR-1 gene and resistance to imatinib in K562 cells

El tratamiento de la Leucemia Mieloide Crónica (LMC) con Imatinib puede fracasar por mutaciones en el dominio tirosina quinasa o amplificación del gen BCR/ABL. Otros mecanismos de refractariedad pueden deberse a los genes de resistencia múltiple a drogas (MDR). Objetivo: Investigar en la línea celular K562 (LMC resistente al Imatinib), la expresión del gen MDRl y los efectos de su inhibición con Ciclosporina A (CyA). Métodos: Se sintetizó ADNc por retrotranscripción del ARN total y se amplificaron por RT-PCR los genes BCR/ABL y MDRl con primers específicos. Se verificó la expresión de la glicoproteína P-gp (producto del gen MDRl) por inmunohistoquímica con 2 anticuerpos monoclonales (C494 y C2l9). Las células K562 fueron enfrentadas (24hs) con Imatinib (2uM), CyA (3ug/ml), Imatinib+Cy A. Se evaluaron apoptosis con naranja de acridina/bromuro de etidio (microscopía de fluorescencia) y función farmacorresistente de P-gp con Rhodamina-l23 (citometría de flujo). Resultados: La expresión del gen MDRl se confirmó tanto por RT-PCRcomo por inmunhistoquímica. La prueba funcional con Rhodamina-l23 indicó que la P-gp fue inhibida por CyA o hipotermia. El tratamiento con Imatinib+Cy A triplicó el porcentaje de apoptosis comparado con Imatinib solo. Conclusión: El gen MDRl jugaría un rol adicional en la resistencia al Imatinib. La Cy A u otros inhibido res de la P-gp, facilitaría la acción del Imatinib, induciendo mayor porcentaje de apoptosis en células BCR/ ABL positivas.

Amplification of the BCR/ABL fusion gene clustered on a masked Philadelphia chromosome in a patient with myeloblastic crisis of chronic myelocytic leukemia.

Although the chronic phase of chronic myelocytic leukemia (CML) is characterized by the Philadelphia (Ph) chromosome creating a hybrid BCR/ABL gene, additional genetic changes involved in blast crisis are poorly understood. We report a 4-8-fold amplification by tandem duplication of the BCR/ABL fusion gene clustered on a masked Ph chromosome in a 61-year-old male patient with CML in myeloblastic crisis. Our finding suggests that the BCR/ABL amplification may play a role as a novel mechanism in the progression to an aggressive blast transformation in some cases of Ph-positive CML.